Perinatal Pathways: Current Research

OUR RESEARCH

Current projects include:
  • BREAKING THE CYCLE OF INTERGENERATIONAL DISADVANTAGE: NEURODEVELOPMENT AMONG PUERTO RICAN CHILDREN

    (1UG3OD023328-01; Duarte, C., Canino, G.J., Monk, C., Posner, J.(MPI))
    Disadvantage can ensnare families for generations. Existing studies have identified the effects of childhood adversity on neurodevelopment in decrements in cognitive and social outcomes. This timeframe, however, may be too constricted, assiduously focusing on intra-generational effects, while ignoring inter-generational determinants. Considering a child’s own adverse exposures, without noting experiences of adversity in that child’s parents, may obscure intergenerational effects. Within an established, well-characterized, inter- generational and disadvantaged cohort, we aim to determine key factors influencing the cycle of disadvantage in which so many families get caught for generations. Our outcome of focus is neurodevelopment as indexed by executive functions (EF) and MRI measures of related neural substrates. EF dysfunctions are key determinants of subsequent social and occupational challenges. We also examine protective factors that may contribute to breaking this cycle of disadvantage and yield favorable neurodevelopmental outcomes. We would bring to the ECHO consortium a multi-generation, population–based sample of 2,491 Puerto Ricans living in the South Bronx, NY and San Juan, PR. The first generation of the cohort (G1) was assessed prospectively at 3 times points in childhood/early adolescence (ages 5-13) and once in late adolescence/early adulthood (ongoing). When ECHO is launched, G1 will be in early adulthood, and just beginning to have their own children (Generation 2 or G2 Probands). Our cohort is thus optimally poised to examine the effects of adversity during early childhood using a prospective design. We will assess G2 Probands including all new births during the study period (Prenatal/Birth Cohort, n~650) and all G2 Proband children born prior to the start of ECHO (Child Cohort, ages 3-10, n~830). We will use neuroimaging and behavioral assessments to characterize the influence of many forms of adverse exposures (e.g., physical abuse, neglect, parental mental illness). We will examine how one generation’s experience of adversities may affect the development of the next, and how different sources of exposure, those experienced by one’s parents as well as those a child faces on his or her own, impact neurodevelopmental outcomes. Our multidisciplinary team brings expertise in the epidemiology of disadvantaged populations (MPIs Duarte & Canino), fetal origins of health and disease (MPI Monk), and developmental neuroscience (MPI Posner). In addition to our specific aims, our study will enrich the ECHO consortium by providing biospecimens including DNA, placenta, cord blood, and deciduous teeth. These specimens will allow the ECHO consortium to investigate the influence of genetic and epigenetic factors as well as chemical exposures during early development within a high-risk, but understudied, population. In sum, our investigative team, the uniqueness of our cohort, and the novelty of our focus on intergenerational influences offer distinct contributions to the ECHO project both in terms of the specific aims of our proposal and to the larger goals of the ECHO consortium.

  • EXPOSOME CONTRIBUTORS TO CHILD HEALTH ORIGINATING FROM NATIONAL FETAL GROWTH STUDY (ECHO-NFGS)

    (1UG3OD023316-01; Vena, J.E., Wapner R., Monk C., Werner, E. (Co-Is))
    Animal and epidemiological studies show that many maternal prenatal experiences (e.g., poor nutrition, stress, elevated environmental pollutants) support the `fetal origins of health’ model in relating adverse maternal experiences to compromised child development. The proposed study leverages the unique resources of the National Fetal Growth Study (NFGS), a cohort of 2397 racially, ethnically and geographically diverse otherwise healthy women and fetuses studied repeatedly during pregnancy. The NFGS included collection of serial ultrasound examinations; maternal anthropometry; stress, physical activity and diet questionnaires; as well as blood samples for serum lipids, cotinine, caffeine, trace elements and persistent environmental pollutants (POPs) many of which have endocrine disrupting and neurotoxic properties with the overall goal of significantly improving our understanding of the associations between maternal prenatal exposures, fetal developmental trajectories, and childhood health outcomes. In the first two years (UG3 phase), we will focus on the key outcome areas of obesity, metabolic health and neurodevelopment demonstrating our ability to re-contact, consent, collect retrospective data on growth, medical diagnoses and residential histories and begin follow-up of the NFGS children who will be ages 3-7 in 2017. We will participate in the ECHO consortium and data collection for the broader ECHO study. In the subsequent five years (UH3 phase), we will continue to follow the children to examine a range of exposures and trajectories of fetal development in relationship to childhood metabolic and endocrine health and neurobehavioral outcomes. We will use innovative statistical modeling to develop functional standards that predict risk of childhood metabolic disruption/obesity and neurobehavioral symptoms based on fetal development trajectories and in utero exposures. The ECCHO-NFGS cohort is unprecedented in its prospective detailed assessment of maternal exposures and quality controlled measures of fetal development throughout pregnancy, in the size of its cohort representing 4 races and 10 geographic locations in the United States, and in its representation of pregnant women recruited as a standard pregnant population free of any identifiable medical or obstetrical morbidities. We will evaluate detailed clinical information, continuous assessments of exposome markers of tremendous relevance during pregnancy (nutrition, stress, physical activity, medication and environmental exposures, etc.) as well as highly accurate measures of fetal growth trajectories in relationship to childhood health outcomes. It is clear that the prenatal period influences children’s health; follow up of this cohort will allow for an unparalleled opportunity to discover how and why.

  • PRENATAL STRESS: THE EPIGENETIC BASIS OF MATERNAL AND PERINATAL EFFECTS

    (R01MH092580; Monk, C., Champagne, F., Tycko, B. (MPI))
    Nearly half of the U.S. population will meet criteria for a psychiatric disorder during their lives, and 1 in 17 has a seriously debilitating illness. Increasingly, these psychopathologies are conceptualized as the late-stage culmination of aberrant developmental processes shaped by a complex interplay of genes and experience, including those occurring in utero. Decades of studies with pregnant animals demonstrate that stress-elicited perturbations in maternal biology affect offspring development, leading to a profile characterized by heightened behavioral and physiologic stress responsivity. Studies of distress in pregnant women, which range from examinations of life stress to psychiatric disorder, largely mirror these findings. Despite ample evidence linking antenatal maternal functioning to offspring outcomes, the mechanistic pathways for this in utero influence on children’s neurodevelopment remain unknown, particularly with human subjects. The burgeoning field of epigenetics — the detection of the molecular effects of environmental experience — has only minimally been applied to pregnant women, yet may provide a vital link in understanding the mechanisms involved in the fetal origins of psychiatric disease risk. The goal of this project is to use recent advances in studying epigenetic gene regulation to identify the biological mechanisms mediating the impact of maternal distress on perinatal development. Aim 1: Determine the influence of pregnant women’s distress on epigenetic gene regulation relevant to perinatal development. Specifically, to establish whether (a) prenatal distress (daily life stress assessed 3x in pregnancy using 24-hour Ecological Momentary Assessment (EMA) via a Personal Digital Assistant (PDA)) and mood symptoms elicited by clinician interviews) predict women’s stress hormone levels (cortisol (from 3x, 12 salivary samples in 48-hours) and CRH (3x blood draws) and gene expression in her PBL (3x blood draws); (b) the timing and degree of women’s altered stress hormone levels and PBL gene expression predict placental gene expression; (c) these mood-dependent biological alterations are associated with the epigenetic mechanism of DNA methylation. Aim 2: Determine perinatal consequences of pregnant women’s distress. Specifically whether, (a) women’s distress-associated altered HPA-axis hormone levels, PBL and placental gene expression/epigenetic variation, predict fetal cord blood gene expression/epigenetic variation, as well as a neurobehavioral profile characterized by heightened reactivity to novelty (fetal and newborn autonomic and central nervous system regulation in response to stimuli). Aim 3: Establish causal influence of epigenetic modification on offspring neurodevelopment. Specifically, using a rodent model in which brain effects of chronic maternal prenatal stress exposure can be directly assessed, we aim to determine (a) the influence of maternal condition on DNA methylation and gene expression in maternal PBLs, placenta, and in the fetal/infant brain and, (b), the relationship between epigenetic variations in these tissues and the development of the postnatal ANS and CNS as indexed by behavioral and stress-hormone responsivity.

  • THE EFFECTS OF PRENATAL STRESS & POOR NUTRITION ON BRAIN AND COGNITION

    (R01MH093677; Monk & Peterson, B. (MPI))
    Children’s neurocognitive development can cast long shadows on their futures, dramatically influencing their occupational functioning and psychosocial adjustment. While it is increasingly recognized that normative varia- tion in early environmental experiences (i.e. parenting style), plays a significant role in shaping cognitive development, evidence indicates that the impact of the environment on cognitive development begins in utero. Two common experiences during pregnancy, psychosocial stress and inadequate micronutrient intake – prominently, iron and zinc, affect outcomes. Prenatal anxiety predicts delayed mental and motor development on the Bayley Scales in infancy, and a reduction in gray matter in the middle temporal lobe based on brain imaging in school-age children. Animal models have demonstrated that antenatal corticosteroid administration is associated with neurocognitive disabilities (i.e. difficulty learning) and structural brain changes such as reduction in hippocampal volume. Infants born to Zinc-deficient mothers show signs of memory impairment. Across both prenatal exposures, what differentiates the animal from the human studies is access to the neonatal brain. The goal of this project is to assess the influence of maternal prenatal stress and poor nutrition on neonatal brain structure and function, and to relate the imaging measures to cognitive outcomes in early childhood. The pro- posed R01 study is a follow-up to an ARRA-funded R01 assessing biopsychosocial stress and nutrition during adolescent pregnancy. Specifically, we have three primary aims to be carried out with pregnant adolescents (ages 15 -19) and their infants: (1) To determine associations between maternal antenatal stress and nutrition, and variation in newborn brain development (from multi-modal imaging). (2) To determine the neural bases of deficits in specific learning and memory tasks, and a general index of cognitive development, associated with prenatal stress and inadequate nutrition. (3) To determine the bidirectional influences between maternal care (i.e. maternal sensitivity and mother-infant attachment style) and infants’ emerging learning and memory capacities. Establishing brain-associated relationships between these prenatal exposures and infant cognition has the potential to help specify the in utero developmental effects of two experiences common to pregnancy, high stress and inadequate nutrition, potentially constraining children’s future learning even before birth. Such results would have significant public health relevance with respect to policy and early intervention approaches. They also could contribute to the identification of exposure-related ‘brain signatures’ to be used for diagnostic and treatment purposes, much as is emerging in imaging studies of depression.

  • EFFECTS OF A MAJOR CLIMATIC EVENT SUPERSTORM SANDY ON PREGNANCY OUTCOMES AND TELOMERE LENGTH

    (R21ES023582; Litvak, P. & Monk, MPI)
    Major climatic events, such as hurricanes, appear to be increasing due to the consequences of global warming. Such events are likely associated with increased psychological stress. On October 29, 2012 Superstorm Sandy, a major hurricane, devastated the mid-Atlantic region of the United States, particularly the New York City/New Jersey area. Pregnant women are considered a vulnerable population and there is increasing evidence that acute psychosocial stressors may be associated with adverse pregnancy outcomes, such as decreases in birth weight and decreases in gestational length. Further, maternal exposure to stressful events may be associated with decreases in leukocyte telomere length (LTL) in the newborn. Capitalizing on a birth cohort currently being recruited, we propose a study to examine associations between exposure to Superstorm Sandy and pregnancy outcomes and newborn LTL. This study improves on previous studies of natural and manmade disasters because we will be able to parse exposure to specific trimesters and to the three months prior to conception; we have place controls, i.e. a cohort being recruited in an unaffected area using exactly the same measures; we have baseline information on maternal perceived stress, depression, anxiety, social support and resilience, and we have an adequate sample size to address the aims. Results from this study have the potential to inform emergency responders and clinicians how best to support and potentially mitigate the effects of psychological stress among pregnant women after a major natural disaster. Results will also set the stage for studies to inquire whether prenatal exposure to stressful events is associated with cognitive and behavioral problems in children.

  • SEROTONERGIC MODULATION OF BRAIN DEVELOPMENT: GENETIC AND PHARMACOLOGIC INFLUENCE

    (P50MH090966; Gingrich, J., PI; Monk, co investigator)
    The current application proposes to create a Silvio O. Conte Center for Basic and Translational Mental Health Research to address the role of serotonin (5HT) signaling in brain development. Before 5HT assumes its canonical role as a neurotransmitter, it acts during early stages of neural growth to exert profound effects on brain structure and function. The Center hypothesizes that two modulators of developmental 5HT signaling include: genetic variants and serotonin selective reuptake inhibitors (SSRIs). In the first case, naturally occurring serotonergic polymorphisms are associated with measurable differences in human brain structure and function. In the second case, the fetus receives incidental exposure from maternal use of SSRI medications. Based on animal models and human imaging, the effects of augmented 5HT signaling on brain development may increase vulnerability to mental disorders as a long-term consequence. The Center will investigate both sources of 5HT signaling modulation and hypothesizes that fetal SSRI exposure and 5HTergic genetic variants will produce convergent effects on brain structure, function, and consequently behavior. The Center includes 4 projects and 4 cores that integrate epidemiology, clinical, and animal models to address the central hypothesis. The Center studies ~11,000 children with in utero exposure to SSRIs by following mental and physical health problems through adolescence. A companion project studies newborns exposed to SSRIs in utero using multi-modal neuroimaging and EEG to assess brain structure and function at the earliest ages. The brain effects of early-life SSRI exposure is studied in mouse models using the same multi-modal imaging measures as well as microscopic analyses of cellular properties that may underlie imaging abnormalities. The Center reasons that the influence of genetic modulators of 5HT is likely encoded during early development. We test this hypothesis through genetically stratified newborns and fetal rhesus macaques, and examining genetics, brain imaging, and EEG in a unique, clinically characterized, population at high and low risk for depression. The Center studies of early-life 5HT signaling and brain development should lead to a better understanding of whether some mental disorders have their origins in development-a question highly relevant to the mission of NIMH.

  • PREPP: PRACTICAL RESOURCES FOR EFFECTIVE POSTPARTUM PARENTING

    (Robin Hood Foundation, formerly R21MH092665; Monk, PI)
    Of the over 4 million live births each year in the United States, nearly 800,000 — or 20% — of the mothers will develop major or minor depression within the first 3 months postpartum. This number dwarfs prevalence rates for gestational diabetes (2-5%) and preterm birth (12.7%). Existing clinical approaches to postpartum depression (PPD) use standard pharmacologic and psychological interventions to reduce women’s symptoms. Nevertheless, PPD is undertreated, in part because women are reluctant to seek treatment due to stigma associated with mental health care and disinclination to take psychotropic medications when breastfeeding. The consequences of this are substantial. Untreated PPD is associated with diminished quality of life and significant emotional suffering for women, and, through compromised caregiving, poor outcomes in children’s cognitive and social-emotional development. Although maternal risk factors for PPD are well known, protocols for prevention based on commonly used depression interventions are only beginning to be evaluated. Building on developmental data showing the profound bi-directionality of emotional and behavioral influences between mother and infant, we propose testing a novel PPD intervention protocol that challenges the standard, individually-focused treatment paradigm. Our intervention is based on the conceptualization of PPD as a potential disorder of the dyad, and one that can be approached through behavioral change in and affective engagement with mother and child. Studies show that infant cry/fuss and sleep behavior are associated with PPD, and that parenting interventions can change infant behavior, yet these findings have never been applied to PPD. In this project, we aim to collect pilot and feasibility data on a novel PPD risk-reducing protocol based on a dyadic behavioral approach to PPD in which we treat at-risk women by promoting maternally-mediated behavioral changes in their infants. We will select a sample of pregnant women at risk for PPD, teach parenting skills to increase infant nocturnal sleep and reduce fuss/cry behavior to half of the sample during 3 perinatal visits, then evaluate infant behavior at 6 and 14 weeks, and maternal mood at 6, 10, and 14 weeks postpartum. In line with NIMH’s strategic goal to develop an integrative understanding of basic brain-behavior processes, we will fully exploit the investigative opportunities of this intervention study by using state-of-the-art EEG and fetal monitoring to characterize early biomarkers associated with infant behavior and behavior change. Our proposal has the potential to have a major impact on clinical research, and to transform the standard care of PPD in that (1) the intervention will have high rates of treatment compliance because (a) the protocol sessions can be incorporated into usual perinatal medical visits, (b) parenting skills will appeal to women as a non-psychiatric intervention, (c) the clinical approach will have face validity given the dyadic focus of the perinatal period; (2) its aim is prevention; (3) it fosters both maternal and child well being; (4) it will expand the risk factors for PPD to include neurobehavioral markers in the perinate.

  • THE LULLABY AND CENTERING PREGNANCY STUDIES

    (Carnegie Hall Musical Connections, The O’Neill Foundation, Monk, PI)
    These are pilot projects assessing the efficacy of two distinct prenatal interventions; the first, the Lullaby project, recruits pregnant women to collaborate with musicians from Julliard and Carnegie Hall in writing their own lullaby. We aim to determine if this unique musical experiences facilitates security in maternal-infant attachment as well as language development in the developing child. The second intervention aims to determine if an evidence-based prenatal curriculum called CenteringPregnancy, a multifaceted model of group care that integrates the three major components of care (health assessment, education, and support), is associated with improved mother–infant attachment as well as healthy neurobehavioral development.

  • THE DOMESTIC VIOLENCE INITIATIVE

    (co directed with Dr. Betsy Fitelson)
    The DVI, a collaborative effort involving the NYC Mayor’s Office to Combat Domestic Violence, the Bronx Family Justice Center, and the Chapman Perelman Foundation, is a pilot project that aims to expand the mental health services available to victims of domestic violence and to engage the community in research aimed at characterizing and preventing the familial transmission of violence.